JP7018387B2 - 腫瘍標的療法のためのｃｘｃｒ６形質導入ｔ細胞 - Google Patents
腫瘍標的療法のためのｃｘｃｒ６形質導入ｔ細胞 Download PDFInfo
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| US20200054677A1 (en) * | 2017-02-21 | 2020-02-20 | The University Of Adelaide | T cells expressing chemokine receptors for treating cancer |
| AU2018248672B2 (en) * | 2017-04-05 | 2021-09-30 | Korea Research Institute Of Bioscience And Biotechnology | NK cell-activating fusion protein, NK cell, and pharmaceutical composition including same |
| US20210002609A1 (en) * | 2017-12-05 | 2021-01-07 | Caribou Biosciences, Inc. | Modified lymphocytes |
| US20210130438A1 (en) * | 2019-10-28 | 2021-05-06 | The Broad Institute, Inc. | Pan-cancer t cell exhaustion genes |
| CN116333999A (zh) * | 2020-07-14 | 2023-06-27 | 广州泛恩生物科技有限公司 | 基于cxcl13阳性t细胞的用于杀伤肿瘤的tcr-t细胞及其制备方法和应用 |
| CN113736740A (zh) * | 2021-07-27 | 2021-12-03 | 天津市肿瘤医院（天津医科大学肿瘤医院） | 胰腺癌稳转细胞系及其构建方法和应用 |
| US20250152629A1 (en) * | 2022-02-15 | 2025-05-15 | Memorial Sloan-Kettering Cancer Center | Compositions including killer innate-like t cells and uses thereof |
Citations (3)
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|---|---|---|---|---|
| US20020076694A1 (en) | 1997-07-17 | 2002-06-20 | Littman Dan R. | G-coupled receptors associated with retroviral entry into cells, and therapeutic uses thereof |
| US20140271635A1 (en) | 2013-03-16 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-cd19 chimeric antigen receptor |
| WO2015028444A1 (en) | 2013-08-26 | 2015-03-05 | Universität Zu Köln | Anti cd30 chimeric antigen receptor and its use |
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| DE19822115B4 (de) | 1998-05-08 | 2004-04-08 | Heinrich-Pette-Institut | Retrovirale Gentransfervektoren |
| US8003770B2 (en) | 2005-09-13 | 2011-08-23 | Mie University | T-cell receptor and nucleic acid encoding the receptor |
| EP2318434A1 (en) | 2008-07-31 | 2011-05-11 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Her2/neu specific t cell receptors |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| ES2696000T3 (es) | 2011-04-08 | 2019-01-11 | Us Health | Receptores de antígenos quiméricos anti-variante III de receptor de factor de crecimiento epidérmico y uso de los mismos para el tratamiento de cáncer |
| EP2768863B1 (en) | 2011-10-20 | 2017-09-27 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Anti-cd22 chimeric antigen receptors |
| AU2013235726B2 (en) | 2012-03-23 | 2017-04-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-mesothelin chimeric antigen receptors |
| RU2650805C2 (ru) | 2012-04-11 | 2018-04-17 | Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретари, Департмент Оф Хелс Энд Хьюман Сёрвисез | Химерные антигенные рецепторы, нацеленные на антиген созревания в-клеток |
| US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020076694A1 (en) | 1997-07-17 | 2002-06-20 | Littman Dan R. | G-coupled receptors associated with retroviral entry into cells, and therapeutic uses thereof |
| US20140271635A1 (en) | 2013-03-16 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-cd19 chimeric antigen receptor |
| WO2015028444A1 (en) | 2013-08-26 | 2015-03-05 | Universität Zu Köln | Anti cd30 chimeric antigen receptor and its use |
Non-Patent Citations (4)
| Title |
|---|
| Journal of Immunology (2008), Vol.181, pp.3099-3107 |
| Journal of Virology (2005), Vol.79, No.3, pp.1686-1700 |
| Nature (1997), Vol.388, pp.296-300 |
| Oncotarget (Mar.29, 2015), Vol.6, No.16, pp.14165-14178 |
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| AU2016336868A1 (en) | 2018-03-15 |
| JP2022008805A (ja) | 2022-01-14 |
| DK3362569T3 (da) | 2021-10-18 |
| CA3001507A1 (en) | 2017-04-20 |
| JP2018531016A (ja) | 2018-10-25 |
| CA3001507C (en) | 2023-09-19 |
| EP3362569B1 (en) | 2021-09-01 |
| EP3362569A1 (en) | 2018-08-22 |
| WO2017064222A1 (en) | 2017-04-20 |
| AU2022205240A1 (en) | 2022-09-29 |
| US20180256645A1 (en) | 2018-09-13 |
| AU2016336868B2 (en) | 2022-04-14 |
| US11723922B2 (en) | 2023-08-15 |
| ES2895901T3 (es) | 2022-02-23 |
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